A transgenic mouse model of the ubiquitin/proteasome system

Nat Biotechnol. 2003 Aug;21(8):897-902. doi: 10.1038/nbt851. Epub 2003 Jul 20.


Impairment of the ubiquitin/proteasome system has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the system are lacking. We have developed a model for in vivo analysis of the ubiquitin/proteasome system by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/proteasome system in physiologic or pathologic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Animals
  • Boronic Acids / pharmacology
  • Cells, Cultured
  • Cysteine Endopeptidases / drug effects
  • Cysteine Endopeptidases / metabolism*
  • Fibroblasts / metabolism*
  • Leupeptins / pharmacology
  • Mice / genetics
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence / methods
  • Models, Animal
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Neurodegenerative Diseases / metabolism
  • Neurons / metabolism*
  • Oligopeptides / pharmacology
  • Organ Specificity
  • Parkinson Disease / metabolism*
  • Proteasome Endopeptidase Complex
  • Recombinant Fusion Proteins / metabolism
  • Tissue Distribution
  • Ubiquitin / drug effects
  • Ubiquitin / metabolism*


  • Boronic Acids
  • Leupeptins
  • MG 262
  • Multienzyme Complexes
  • Oligopeptides
  • Recombinant Fusion Proteins
  • Ubiquitin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • epoxomicin